Significant strides have been made in the treatment of advanced stage cancers over the past few years. One of these advances centers around the introduction of cisplatin into treatment regimens for ovarian cancer. Despite such advances, however, the number of patients experiencing long-term disease-free periods after receiving such platinum-based therapy remains under 20 percent (Young et al., "Cancer Of The Ovary" in Cancer Principles and Practice of Oncology (DeVita et al., Eds., J. B. Lippincott Co., Philadelphia), 1162-96 (1989); Rothenberg et al., Med. J. Australia, 148, 354-63 (1988)). While these results are encouraging, they nevertheless underscore the need for the discovery of more effective agents and regimens useful in treating solid cancerous tumors.
Taxol has been identified as one such new agent. This agent is derived from the bark of the Western Yew tree, taxus brevifolia (Chabner, PPO Update, 5 (9), 1-10 (1991); Rowinsky et al., J. Nat'Cancer Inst., 82, 1247-1259 (1990)). Studies to date have indicated that taxol within a dose range of 110 to 200 mg/m.sup.2 has produced objective responses in about 30 percent of patients having cisplatin-sensitive and cisplatin-resistant advanced stage epithelial ovarian cancer (McGuire et al., Ann. Intern. Med., 11, 273-79 (1989); Thigpen et al., Proceedings ASCO, 9, 156 (Abst. 604) (1990); Einzig et al, Proceedings AACR, 31, 187 (Abst. 1114) (1990)). Indeed, taxol is the only agent with proven efficacy for patients with platinum-resistant ovarian cancer.
However, despite taxol's promise, there is a limit to the amount of taxol that can be used in any treatment regimen. More specifically, when taxol is administered in a treatment regimen for solid tumors, patients experience myelosuppression i.e., bone marrow suppression which includes neutropenia, anemia, and thrombocytopenia, at elevated taxol levels. This myelosuppression is dose-limiting, hence the maximum quantity of taxol that is recommended to be used in the treatment of solid tumors is 175 mg per square meter of body area every 21 days (mg/m.sup.2 / 21 days) (Donehower et al., Cancer Treat. Rpt., 71, 1171-77 (1987); Wiernik et al., Cancer Res., 47, 2486-93 (1987); Wiernik et al., J. Clin. Oncol., 5, 1232-39 (1987)).
Other problems in addition to myelosuppression appear when dosage levels of taxol over the previously identified maximum are administered. As the taxol dosage level is increased to levels above about 175-200 mg/m.sup.2 / 21 days, a further dose-limiting toxicity, mucositis, is encountered. Mucositis is an inflammation of the lining of the gastrointestinal tract which may result in mouth sores, painful diarrhea, and rectal soreness. Eventually, with yet higher dosage levels of taxol, e.g., above about 300 mg/m.sup.2 / 21 days, severe neurotoxicity in the form of peripheral neuropathy is experienced (Rowinsky et al., Cancer Res., 49,4640-47 (1989); Lipton et al., Neurology, 39,368-73 (1989)).
The aforesaid potentially severe consequences which arise when taxol is administered at dosages above about 175 mg/m.sup.2 / 21 days have prevented even the clinical investigation of the therapeutic effect of taxol at dosages in excess of that level.
Accordingly, there exists a need for a means to alleviate or prevent the adverse side-effects attendant the administration of taxol in high doses so as to enable an evaluation of the therapeutic effects of taxol at dosage levels above the dose-limiting amount presently able to be safely administered. Similarly, there is a need for a method of providing a relatively safe and effective regimen using taxol for the treatment of cancerous solid tumors, particularly ovarian tumors, without the attendant side-effects of myelosuppression, mucositis, and other toxicities.
These needs are satisfied with the method of the present invention. In particular, it is an object of the present invention to provide a means of enabling the evaluation of the therapeutic benefits of taxol while alleviating or preventing myelosuppression, mucositis, and other toxicities. It is a further object of the present invention to provide a safe and effective regimen utilizing taxol for the treatment of cancerous tumors.
These and other objects and advantages of the present invention, as well as additional inventive features, will be apparent from the description of the invention provided herein.